中国汉族群体中PDCD1基因多态性与结直肠癌的相关性CSCD

目的探讨程序性细胞死亡受体1（ programmed cell death 1,PDCD1）基因多态性与结直肠癌的发生发展的关联性。方法应用聚合酶链反应-限制性片段长度多态性（PCR-restriction fragment length polymorphism, PCR-RFLP）方法对426例结直肠癌患者及500名正常个体的rs36084323、rs11568821、rs2227981、rs2227982和rs10204525位点进行多态性分析。结果rs36084323位点G等位基因在显性遗传模型下与TNM分期进展期结直肠癌的发生正关联（OR＝1.59,95%CI：1.02～2.48）。rs36084323、rs11568821、rs2227981、rs2227982和rs10204525位点组成的单倍型G-G-C-T-A和A-G-C-C-G与结直肠癌的发生负关联。结论PDCD1基因rs36084323位点AG和GG基因型与TNM分期进展期的结直肠癌存在正关联。而G-G-C-T-A和A-G-C-C-G单倍型与结直肠癌的发生负关联。     

Genetic polymorphism and relationship of 24 Y-STR loci among three ethnic minorities from GuizhouCSCD

Objective: To study the distribution of haplotypes of Y-chromosomal short tandem repeats (Y-STR) loci among three ethnic minorities from Guizhou, China. Methods: Twenty four Y-STR loci of 174 unrelated males were amplified with a Microreader™ 24Y Direct ID System kit. Capillary electrophoresis was carried out on an ABI 3100 Genetic Analyzer, and the data was analyzed with GeneMapper software. Results Seventy six haplotypes were identified for the 24 Y-STR loci among the three ethnic minorities, including 13 from the Qiangs, 35 from the Manchurians, and 28 from the Shes, with the corresponding Haplotype Diversity (HD) being 0. 7327, 0. 9578, and 0. 9344. Genetic distance between the Shes and Qiangs was relatively close, whilst that for Manchurians was relatively far. Conclusion: Analysis of the genetic characteristics and relationship of the three ethnic minorities from Guizhou can provide a reference for the study of their origin, evolution and patrilineal fusion. © 2018 MeDitorial Ltd. All rights reserved.     

Allelic resolution NGS HLA typing of Class I and Class II loci and haplotypes in Cape Town,South Africa

The development of next-generation sequencing (NGS) methods for HLA genotyping has already had an impact on the scope and precision of HLA research. In this study, allelic resolution HLA typing was obtained for 402 individuals from Cape Town, South Africa. The data were produced by high-throughput NGS sequencing as part of a study of T-cell responses to Mycobacterium tuberculosis in collaboration with the University of Cape Town and Stanford University. All samples were genotyped for 11 HLA loci, namely HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1, -DRB3, -DRB4, and -DRB5. NGS HLA typing of samples from Cape Town inhabitants revealed a unique cohort, including unusual haplotypes, and 22 novel alleles not previously reported in the IPD-IMGT/HLA Database. Eight novel alleles were in Class I loci and 14 were in Class II. There were 62 different alleles of HLA-A, 72 of HLA-B, and 47 of HLA-C. Alleles A123:17, A143:01, A129:11, A168:27:01, A101:23, B114:01:01, B115:10:01, B139:10:01, B145:07, B182:02:01 and C108:04:01 were notably more frequent in Cape Town compared to other populations reported in the literature. Class II loci had 21 different alleles of DPA1, 46 of DPB1, 27 of DQA1, 26 of DQB1, 41 of DRB1, 5 of DRB3, 4 of DRB4 and 6 of DRB5. The Cape Town cohort exhibited high degrees of HLA diversity and relatively high heterozygosity at most loci. Genetic distances between Cape Town and five other sub-Saharan African populations were also calculated and compared to European Americans.     

HLA -A, -C, -B, -DRB1, -DQB1 and -DPB1 allele and haplotype frequencies in 4514 healthy Norwegians

We report HLA-A, -C, -B, -DRB1, -DQB1 and -DPB1 allele frequencies and estimated haplotype frequencies from 4514 healthy Norwegians who volunteered to participate in the Norwegian Bone Marrow Donor Registry. HLA genotyping was conducted on a Next Generation Sequencing platform. Data were analyzed using Arlequin and Pypop software. No significant deviations from Hardy-Weinberg Equilibrium were noted at any of the loci studied. We discuss the representability for the Norwegian population and argue that the presented HLA data could serve as a Norwegian reference panel.     

A European HLA Isolate and Its Implications for Hematopoietic Stem Cell Transplant Donor Procurement

Europeans have often been considered a homogenous group in registry donor match predictions, but it is now evident that HLA haplotype frequencies vary across the European continent. Earlier studies have indicated that Finns in northeastern Europe have unique HLA characteristics, and the increasing availability of high-resolution registry donor data is now making more detailed comparisons possible. In the first phase of the present study, estimated HLA haplotype frequencies in stem cell donor registries of Finland and its neighbors Sweden and Russia were calculated using the algorithm of the German National Bone Marrow Donor Registry (ZKRD) and their frequencies were compared with one another and also with that of Germany. Virtual donor searches for 1492 high-resolution typed Finnish patients in the Finnish, Swedish and German registries were then performed, using individual match predictions for each registry. In the last phase, the impact of specifically Finnish-enriched HLA haplotypes on Finnish patients and the use of Finnish registry donors was assessed by analyzing 647 consecutive hematopoietic stem cell transplantation (HSCT) donor searches and 40 exported Finnish HSCTs. The Finnish HLA landscape was more homogenous than the 3 other studied populations, but also genetically distinct from them. The match predictions found a probable 10/10 match for 71%, 41%, and 31% of the Finnish patients in the German, Finnish, and Swedish registries, respectively. Thirty-four of Finland's 100 most frequent HLA haplotypes were represented with a frequency of <.0003 in Germany, and with an 8- to 3262-fold greater frequency in Finland than in Germany. Patients carrying these Finnish-enriched haplotypes were less likely to receive a matched HSCT but more likely to receive it from a domestic donor. Registry donors carrying them were more likely to donate stem cells, both nationally and internationally. The Finnish HLA isolate has a significant impact on both Finnish patients and registry donors, explaining the high use of national registry donors for Finnish patients. Haplotype frequency estimations are an important tool for small registries as well, to help optimize donor match predictions and the size of individual registries.     

多药耐药基因多态性和单倍体对环孢素A血药浓度的影响

目的探讨中国健康志愿者中多药耐药基因(MDR1)12外显子C1236T、21外显子G2677T/A和26外显子C3435T多态性及3个位点单倍体连锁不均衡性对环孢素A(CsA)药代动力学特性的影响。方法高效液相色谱法(HPLC)测定20名健康男性单次口服CsA500mg后,24h中不同时间点的血药浓度。采用聚合酶链反应(PCR)结合基因测序法测定3个位点的基因多态性和单倍体类型。结果20名男性健康志愿者中,C1236T位点1名为CC型,8名为CT型,11名为TT型;G2677A/T位点4名为GG型,7名为GT型,4名为AT型,5名为TT型;C3435T位点5名为CC型,11名为CT型,4名为TT型;MDR1的C1236T和G2677A/T的基因多态性与峰浓度(Cmax)和药时曲线下面积(AUC0inf)差异均无统计学意义(均P>0.05),C3435T的基因多态性与Cmax无相关性(P>0.05),而与AUC0inf相关(P<0.05)。CC型、CT型和TT型的Cmax分别为2124.7±179.4ng/ml、1934.2±372.8ng/ml和1765.2±415.6ng/ml;AUC0inf分别为13922.4±2881.5ng/h-1·ml、11511.8±2192.1ng/h-1·ml和8514.9±1063.4ng/h-1·ml;至少含有1个C等位基因的基因型(CC型和CT型),二者的AUC0inf比TT型增高49%。单倍体分析表明,26与12和21外显子间存在单核苷酸多态性的连锁不均衡性,不同单倍体类型对CsA药动力学特性无影响(P>0.05)。结论MDR1C3435T的多态性可能是口服CsA后,生物利用度变异大的影响因素。     

Genetic variants in the CPNE5 gene are associated with alcohol dependence and obesity in Caucasian populations

Alcohol addiction may increase the risk of obesity due to shared genetic components. The Copine V (CPNE5) gene is involved in Ca²⁺ binding and may play an important role in the development of the central nervous system. This study tested the genetic associations of 77 single-nucleotide polymorphisms (SNPs) within the CPNE5 gene with alcohol dependence (AD) and obesity using a Caucasian sample – The Study of Addiction – Genetics and Environment (SAGE) sample (1066 AD cases and 1278 non-AD controls, 422 obese cases and 1395 non-obese controls). The Marshfield sample (1442 obese cases and 2122 non-obese controls) was used for replication of obesity. Multiple logistic regression analysis was performed using the PLINK software. In the SAGE sample, we identified 10 SNPs associated with AD and 17 SNPs associated with obesity (p < 0.05). Interestingly, 6 SNPs (rs9986517, rs9470387, rs3213534, rs10456444, rs3752482, and rs9470386) were associated with both AD (OR = 0.77, 0.77, 0.83, 0.84, 0.79 and 1.14, respectively; p = 9.72 × 10⁻⁵, 1.1 × 10⁻⁴, 4.09 × 10⁻³, 5.26 × 10⁻³, 1.59 × 10⁻², and 3.81 × 10⁻², respectively) and obesity (OR = 0.77, 0.77, 0.78, 0.77, 0.68 and 1.18, respectively; p = 2.74 × 10⁻³, 2.69 × 10⁻³, 2.45 × 10⁻³, 1.01 × 10⁻³, 5.18 × 10⁻³ and 3.85 × 10⁻², respectively). In the Marshfield sample, rs3752480 was associated with obesity (p = 0.0379). In addition, four SNPs (rs9986517, rs10456444, rs7763347 and rs4714010) showed associations with obesity in the meta-analysis using both samples (p = 0.00493, 0.0274, 0.00346, and 0.0141, respectively). These findings provide the first evidence of common genetic variants in the CPNE5 gene influencing both the AD and obesity; and will serve as a resource for replication in other populations.     

High-resolution HLA-A,HLA-B,and HLA-DRB1 haplotype frequencies from the French Bone Marrow Donor Registry

We have estimated human leukocyte antigen (HLA) haplotype frequencies using the maximum likelihood mode, which accommodates typing ambiguities. The results of the frequency distribution of the 7015 haplotypes obtained are presented here. These include a total of 114 HLA-A, 185 HLA-B, and 76 HLA-DRB1 unique alleles at each locus. Across all populations, although the most common individual HLA alleles were HLA-A¹02:01 (29.0%), HLA-B¹07:02 (11.4%), and HLA-DRB1¹07:01 (15.9%), the most frequent haplotype was found to be HLA-A¹01:01∼B¹08:01∼DRB1¹03:01.